Airline bmi is to terminate its daily return service between Inverness and London Heathrow because of a lack of bookings.
The airline will suspend the service from 29 March
The company said flights on the route, which was launched in March 2004, would end on 29 March.
Lib Dem MP Danny Alexander said it was a "disgraceful decision" to close the city's only link to Heathrow.
Scottish Transport Minister Stewart Stevenson is seeking a meeting with the airline to urge a rethink on the move.
Mr Stevenson said: "The Inverness and Highland business community fought long and hard to get a service to Heathrow reinstated following British Airways withdrawal in 1997.
"It is also particularly disappointing, given Highlands and Islands Airports efforts to achieve a better scheduling of the service, which would have gone a long way to improving its viability."
Flybe and Easyjet fly to Gatwick and Easyjet also runs services to Luton.
Mr Alexander, MP for Inverness, Nairn, Badenoch and Strathspey, said it was now essential to protect the Highlands' links with Gatwick.
The MP said bmi had repaid the loyalty of its Inverness customer base with "a slap in the face".
Mr Alexander claimed the suspension was a direct result of European Union transport ministers' unanimous backing for an "open skies" aviation deal with the US.
Inverness also has links to Gatwick and Luton
The agreement is aimed at liberalising transatlantic air travel and eases restrictions on travel between Europe and the US.
This has put pressure on the flight slots available at Heathrow.
Future bookings on the Inverness-Heathrow route indicated there was little prospect for sufficient improvement in its performance, according to bmi.
The airline said charges such as air passenger duty had led to higher fares.
Peter Spencer, managing director of bmi, said: "We are very disappointed that there has been insufficient demand to operate a viable profitable operation but load factors have not been sufficiently high enough to sustain the service."
He added: "We acknowledge the efforts that Inverness Airport have made to assist bmi in the continuation of the route through the level of fees at Inverness Airport."
Inglis Lyon, managing director of Highlands and Islands Airports, said bmi's decision was disappointing, but not surprising because of pressures on slots at Heathrow.
He said: "We have worked very hard with bmi to maintain the Heathrow link which is an important one for our region."
Mr Lyon added: "Fortunately, at Inverness, we are still well served with links to Gatwick and Luton.
"We are also talking to operators regarding potential new London services, with London City a target for development."